OBJECTIVES: a) We will continue our investigation of the coupling of translation and transcription in permeabilized cells of B. subtilis, with particular reference to the nucleotide effectors which may (?) underly this relationship. We will also investigate the mechanisms by which the stringent response of B. subtilis elicits the accumulation of the six unusual nucleotides, tentatively characterized, which are putative regulatory signals. b) We will continue our studies of the relationship between stringent control in E. coli and regulation of translational accuracy. In cell free systems, we will investigate the effects of pppGpp and of other ribosome inhibitors on the translation of synthetic and natural messengers, examining both amino acid substitution errors and translocation (frameshift) errors. In whole cell experiments, we will enlarge our studies of phenotypic suppression of nonsense and frameshift alleles, concentrating on those cases (especially rIIB) mutants of phage T4) where there is sufficient sequence information to permit the formulation of questions pertaining to the codon specificity of mistranslation. c) We have conducted preliminary studies of error propagation in a simple eukaryote (yeast). We contemplate following these studies up, and perhaps extending them to other eukaryotic systems, but this work is not in progress at the moment.